DESCRIPTION: (provided by the applicant) Cognitive impairment is a common and clinically significant symptom of human immunodeficiency virus (HIV). Approximately 30-87 percent of individuals with HIV experience cognitive difficulties. Highly active antiretroviral (HAART) medications are effective in treating the peripheral symptoms of the disease, and recent evidence suggests that the benefits may extend to the central nervous system. This treatment effect may not occur in some populations of patients, such as substance abusers. HIV is acquired through substance abuse in approximately 50 percent of cases, and many individuals continue to abuse drugs after learning of their HIV status. In our own analyses of the HERS data, we found that women who reported a recent history of injection drug use continued to exhibit cognitive decline despite receiving HAART, while non-abusers showed significantly less decline. Drug type was not specified, but abuse of cocaine may be specifically associated with impaired cognition in HIV. Cocaine increases the permeability of the blood brain barrier, impairs immunoreactivity, and increases vascular complications. The purpose of the present study is to examine cognitive function in HIV-infected women who abuse cocaine in addition to other substances, women that do not abuse cocaine but do abuse other substances, and a healthy control group. The three groups will be administered a battery of cognitive measures sensitive to HIV-associated impairments. MANOVAs will contrast group performance on the cognitive measures. CD4 status, mood, and ratings of fatigue will be covaried. I expect to demonstrate that HIV-positive women who abuse cocaine will exhibit significantly poorer cognitive function compared to the other two groups. This effect will not be due to differential immune system status, depression, or mental fatigue. Results from the study will extend our understanding of the factors that affect cognition in HIV. In addition, the data from this R03 will serve as important pilot data for a more comprehensive study of cognitive function in HIV-positive substance abusers.